Experimental evidence of interleukin-2 activity in bone marrow transplantation.
OBJECTIVE
This article reviews the preclinical and clinical experience with the administration of recombinant interleukin-2 (rIL-2) and rIL-2-activated lymphocytes following allogeneic or autologous bone marrow transplantation in patients with hematologic malignancies and advanced breast cancer.


METHODS
Recombinant IL-2 was administered following engraftment of bone marrow or peripheral blood stem cell. (PBSC) transplants to enhance the graft versus tumor effect. Ex vivo incubation of bone marrow or PBSC with rIL-2 was used to activate effector lymphocytes (i.e., T cells and natural killer cells) that may enhance the antitumor effect.


RESULTS
We have shown in preclinical models that the incubation of bone marrow or PBSC in rIL-2 generates cytotoxic effector cells that are capable of lysing a wide variety of tumor cells. In those models we have also found that these same rIL-2-activated cells are able to induce a syngeneic graft-versus-host disease (GVHD) that correlates with the antitumor effect. We have now taken this concept into the clinic in patients with hematologic malignancies and advanced breast cancer. We have treated patients with stage II through stage IV breast cancer with PBSC that have been incubated with rIL-2. We have now reached a stable phase II dose of rIL-2 with no adverse effect on engraftment. We have found that cytotoxic cells are generated in the patients' circulation, and that these cells are activated T cells, not natural killer cells. Approximately 50% of the patients seem to have autologous GVHD. Patients with stage II breast cancer seem to generate more cytotoxic cells than patients with stage IV breast cancer. We are in the process of examining whether these patients have an increased disease-free survival.


CONCLUSIONS
We have shown that rIL-2-activated cells seem to generate autologous GVHD and possibly induce a graft-versus-tumor effect. Use of similar approaches in BMT will be important in the future to generate similar types of immune antitumor effects.
Mazumder
A
A
Bone Marrow Transplant Unit, University of Miami School of Medicine, FL 33136, USA.
D001943:Breast Neoplasms / Q000628:therapy; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000502:physiology; D008213:Lymphocyte Activation; D011994:Recombinant Proteins / Q000494:pharmacology
D007376:Interleukin-2; D011994:Recombinant Proteins